Prognostic values of B-type natriuretic peptide in severe sepsis and septic shock* Anthony S. McLean, MB ChB, FRACP, FJFICM; Stephen J. Huang, PhD; Stephanie Hyams, MB BS; Genie Poh, MB BS; Marek Nalos, MD; Rahul Pandit, MD; Martin Balik, MD; Ben Tang, MB BS; Ian Seppelt, MB BS, FANZCA, FJFICM T he cardiac ventricles are the main source of circulating B- type natriuretic peptide (BNP) in humans. The stimulus for BNP release is ventricular wall stretch, as a result of either volume expansion or pressure overload (1). BNP levels are el- evated in patients with symptomatic left ventricular dysfunction and correlate with filling pressures (2, 3). The levels are also associated with higher mortality rates in patients with heart failure (4). The activation and release of BNP are believed to be a mechanism to counter- regulate the maladaptive responses of the renin-angiotensin-aldosterone and the sympathetic systems in heart failure (5). BNP has a fundamental role in cardiovas- cular remodeling, volume homeostasis, and the response to ischemia (6, 7). The release of BNP is associated with im- provements in cardiovascular hemody- namics, including reduction of preload and afterload (8). BNP has been used to screen for car- diac dysfunction in the intensive care set- ting. The mean admission plasma BNP level was found to be eight- to nine-fold higher in intensive care patients with car- diac dysfunction than those without (9). However, BNP was also found to be ele- vated in sepsis (10, 11). Interestingly, some septic patients with elevated BNP levels did not display any cardiac dysfunc- tion (12). Sepsis is a major cause of death in the intensive care unit (ICU) and the commu- nity. Between 11% and 15% of patients admitted to ICUs have or develop severe sepsis, and the mortality rate for these patients varies between 30% and 60% (13–15). In the United States, severe sep- sis accounts for 215,000 deaths per year, and the mortality rates ranged from 25% to 80% (16). In Australia and New Zea- land, approximately 12% of patients ad- mitted to ICU were diagnosed with severe sepsis. The mortality rate for these pa- tients reached 26.5% and 37.5% in ICU and in hospital, respectively (17). Much effort has been used to identify the factors that can predict mortality in sepsis. Some of these factors include age, physiologic and laboratory values, serum high-density lipoprotein cholesterol lev- els, immunosuppression, clinical signs of lung consolidation, sepsis-related organ failure assessment scores, and sepsis- related reversible myocardial depression (18 –22). However, the performance of many of these variables is unsatisfactory. Given that BNP levels are related to cardiovascular functions and hemody- namics, which are both compromised in *See also p. 00. From the Department of Intensive Care Medicine, University of Sydney, Nepean Hospital, Sydney, NSW, Australia. Dr. Balik’s current address is Department of An- aesthesia and Intensive Care, General Faculty Hospital, Prague, Czech Republic. The authors have not disclosed any potential con- flict of interest. Address requests for reprints to: Anthony S. McLean, MD, Department of Intensive Care Medicine, Nepean Hospital, University of Sydney, PO Box 63, Penrith, NSW 2751, Australia. E-mail: mcleana@ med.usyd.edu.au Copyright © 2007 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/01.CCM.0000259469.24364.31 Objective: To investigate the changes in B-type natriuretic peptide concentrations in patients with severe sepsis and septic shock and to investigate the value of B-type natriuretic peptide in predicting intensive care unit outcomes. Design: Prospective observational study. Setting: General intensive care unit. Patients: Forty patients with severe sepsis or septic shock. Interventions: None. Measurements and Main Results: B-type natriuretic peptide measurements and echocardiography were carried out daily for 10 consecutive days. In-hospital mortality and length of stay were recorded. The admission B-type natriuretic peptide concentra- tions were generally increased (747  860 pg/mL). B-type natri- uretic peptide levels were elevated in patients with normal left ventricular systolic function (568  811 pg/mL), with sepsis- related reversible cardiac dysfunction (630  726 pg/mL), and with chronic cardiac dysfunction (1311  1097 pg/mL). There were no significance changes in B-type natriuretic peptide levels over the 10-day period. The daily B-type natriuretic peptide con- centrations for the first 3 days neither predicted in-hospital mor- tality nor correlated with length of intensive care unit or hospital stay. Conclusion: B-type natriuretic peptide concentrations were increased in patients with severe sepsis or septic shock regard- less of the presence or absence of cardiac dysfunction. Neither the B-type natriuretic peptide levels for the first 3 days nor the daily changes in B-type natriuretic peptide provided prognostic value for in-hospital mortality and length of stay in this mixed group of patients, which included patients with chronic cardiac dysfunction. (Crit Care Med 2007; 35:1019–1026) KEY WORDS: B-type natriuretic peptide; severe sepsis; intensive care; cardiac dysfunction; mortality; length of stay balt4/zrz-ccm/zrz-ccm/zrz00407/zrz7536-07z xppws S1 3/1/07 8:28 Art: CCM181849 1019 Crit Care Med 2007 Vol. 35, No. 4 Abst